Neurotransmitters in opiate and alcohol addiction

Lead Research Organisation: University of Bristol
Department Name: Department of Psychopharmacology

Abstract

Heroin and alcohol addiction have massive impacts on modern society, causing severe medical, psychological and social problems with their associated costs including increased use of medical resources, lost working hours and increases in crime and public disorder. In the last two decades there has been a big increase in the number of people addicted to drugs and alcohol but treatments have not kept pace with this. To try to improve this situation we are working to understand the brain processes that lead to addiction. We know that drugs including alcohol act by changing chemical messengers in the brain called neurotransmitters. Our study tries to show how these are altered in people addicted to heroin or alcohol. We also want to understand how treatments work, so we also study the effects that current treatments have in the brain to help design new and better ones.

This work will continue our successful previous research which uses the newest scanning technique, positron emission tomography (PET). This allows us to directly measure levels of neurotransmitters and their receptors in the human brain. We focus on three key neurotransmitters in addiction- the dopamine system involved in mediating pleasure, the opiate system which mediates many effects of opiate drugs such as heroin and also the pleasurable effects of alcohol, and lastly the GABA system, the brain?s natural calming system that mediates many effects of alcohol.

We rely on our patients or users to volunteer for our studies and we regularly meet with them to inform them about how the research is going and to discuss with them interpretation and relevance of the results.

As well as publishing our work in scientific journals and giving presentations at national and international conferences we also give lectures to the public about our research and the science underpinning it. Bristol University is committed to public education in science and has a Professor specifically for this ? the Collier Professor of Public Understanding of Science (at present Kathy Sykes of BBC s Rough Science). She has already worked with us in several local community meetings on addiction. Members of our research team often appear on local and national radio and TV to talk about advances in understanding of addiction, and take part in meetings with school children and their parents to give guidance on risks and realities of drug and alcohol use.

Technical Summary

This is a major 5-year grant that uses state-of-the-art PET neuroimaging plus pharmacological challenge and gene analysis to test critical theories about brain mechanisms that underlie addiction to, and pleasure from, alcohol and opiates (heroin). The role of three key neurotransmitter and receptor systems will be evaluated:? GABA, dopamine and endogenous opioids (endorphins) using PET tracers, 11C-Ro 15-4513 and 11C-flumazenil for GABA-A, 11C-raclopride for dopamine and 11C-diprenorphine for the opioid system. Specifically we shall test the following theories that
1) GABA
a) the alpha5 subtype of the GABA-A receptor is involved in alcohol and opiate dependence
b) the new selective tracer 11C-Ro15-4513 can be used to measure synaptic GABA concentrations in living human brain, to allow investigation of whether alcohol increases GABA function.
2) Dopamine
a) the release of dopamine in the striatum relates to the expectation of heroin and not to its direct pharmacological action
b) the lower the density of dopamine D2 receptors the greater the pleasurable effect of substances
c) alterations in brain endorphin systems are a common feature of withdrawal from both opiates and alcohol and contribute to craving and relapse.

Publications

10 25 50
 
Description mrc
Geographic Reach National 
Policy Influence Type Membership of a guidance committee
Impact showed applicaitons and opportunities for translational research
 
Title pet tracer 
Description vlaidation of 11C-ro154513 as an alpha-5 selctive GABA-A receptor tracer in humans 
Type Of Material Physiological assessment or outcome measure 
Provided To Others? No  
Impact lower binding in the brainms of alcoholics especially in brain regions relating to addiction and memory 
 
Description Disseminating information about the MARC scheme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented MARC scheme, its aims and opportunities. Presented at RCPsych Addictions Faculty Meeting 2016 as well as other regional meetings alongside presentation of research outputs from other grants
Year(s) Of Engagement Activity 2015,2016
URL http://www.imperial.ac.uk/medicine/mrc-addiction-research-clinical-training/
 
Description Keynote Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact To present a talk at the Spanish Academy of medicine to an audience of Spanish medical staff.
Year(s) Of Engagement Activity 2017
 
Description presentation at CFS meeting in 2016\ 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact british sleep society meeting

more interviews - and public lectures eg cafe scientifiques
Year(s) Of Engagement Activity 2016